BREAKING! COVID-19 Immunology: Qatar Research Finds That Coronavirus Antibodies From Children Differs From Adults And Offers Broader Protection
: Medical and immunology researchers from Qatar have discovered that antibody performances against endemic human coronaviruses are qualitatively different in children when compared to the general adult population, as well as healthy adult blood bank donors and they may also provide cross-protection against epidemic/pandemic strains.
So far four endemic human coronaviruses are frequently associated with respiratory illness in humans, rarely causing anything more serious than a common cold. However, in addition to these 'benign' species, three epidemic coronaviruses have emerged in humans over the last two decades. These include severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and now severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the etiological agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic.
Numerous studies have suggested that endemic human coronaviruses can induce broadly cross-reactive T cell responses, affecting clinical outcomes of acute infections with the phylogenetically related epidemic viruses (namely MERS-CoV and SARS-CoV-2).
However to date, a systematic appraisal to elucidate immunodominant B cell antigen determinants of endemic human coronaviruses, their degree of representing cross-reactive antigenic sites, as well as the variation in the cellular and humoral immune responses among humans of different age has not yet been done.
Researchers from Sidra Medicine, Qatar University, Weill Cornell Medical College in Qatar and Hamad Bin Khalifa University in Doha, Qatar recently conducted a comprehensive retrospective analysis of coronavirus-specific antibodies in a large number of samples from children and adults.
Their research findings that is yet to have been peer-reviewed is published on a pre-print server and provides a new and interesting insight. https://www.biorxiv.org/content/10.1101/2020.06.21.163394v1
In order to obtain a more in-depth insight into human antibody responses to endemic human coronaviruses, the researchers performed Phage-Immunoprecipitation Sequencing (PhIP-Seq) on serum or plasma samples collected before COVID-19 pandemic from a large number of individuals in three different study cohorts.
These cohorts included healthy male adult blood donors with diverse ethnic backgrounds, adult male and female participants of a national cohort study known as the Qatar Biobank, as well as pediatric inpatients and outpatients. They were all tested for metabolic conditions unrelated to infection, malignancies, or chronic diseases.
With the use of PhIP-Seq, comprehensive antiviral antibody repertoires were gathered across individuals in these three human cohorts by phage display of oligonucleotide-encoded peptidomes, which was followed by immunoprecipitation and massive parallel sequencing.
The obtained seroprevalence of endemic coronaviruses were assessed in the three cohorts separately by imputing species score values via
counting significantly enriched peptides for a given coronavirus species that share less than seven amino acids linear sequence identity.
This resulting comprehensive screen for antiviral antibody repertoires across three distinct human cohorts revealed a large number of peptides that exhibit novel linear epitopes in several proteins of endemic human coronaviruses. Among them, there were 25 new immunodominant linear B cell epitopes.
By using stringent and robust cut-off values, the researchers have also estimated that the seroprevalence of endemic human coronaviruses ranges from approximately 4% to 27%, depending on the species and studied cohort.
Significantly, a surprising and somewhat unexpected finding of this study was that circulating IgG antibodies in pediatric subjects (when compared to the adult ones) differentially targeted structural and non-structural proteins of human coronaviruses.
It was found that the antibodies in children showed affinity towards structural proteins such as nucleocapsid protein and spike glycoprotein. At the same time, in adults, specific regions of the non-structural polyprotein known as 'pp1ab' were their primary target.
In addition, some antibodies were found to be broadly cross-reactive with peptides of epidemic human and non-human coronavirus isolates, which may play a protective role against endemic and epidemic infections particularly among children that seem to target such functionally relevant B cell epitopes and seldom present with severe disease outcomes.
Professor Dr Nico Marr from College of Health and Life Sciences, Hamad Bin Khalifa University, Doha- Qatar, the corresponding author of the study told Thailand Medical News, "Information about the targets of immune responses to coronaviruses across different species provides a valuable resource for the prediction of candidate targets of newly emerging coronaviruses."
These new research findings elucidate the humoral immune responses to natural infection with endemic human coronaviruses and may have important implications for understanding highly variable clinical outcomes seen in human infections. But there is also an issue of cross-reactivity.
Professor Dr Taushif Khan from the research department at Sidra Medicine, Doha-Qatar said, "It is tempting to speculate that natural infection with endemic human coronavirus may provide some degree of cross-protection and may, therefore, affect health outcomes in individuals infected by epidemic coronaviruses, such as SARS-CoV-2 or MERS-CoV.”
Thailand Medical News would hopefully like to see the findings of this study helping to propel further research and lead to further development of prophylactic or therapeutic monoclonal antibodies and vaccine design, with potential broad-spectrum activity against many different coronaviruses.
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